Thirst and Drinking Paradigms: Evolution from Single Factor Effects to Brainwide Dynamic Networks

Abstract

The motivation to seek and consume water is an essential component of human fluid–electrolyte homeostasis, optimal function, and health. This review describes the evolution of concepts regarding thirst and drinking behavior, made possible by magnetic resonance imaging, animal models, and novel laboratory techniques. The earliest thirst paradigms focused on single factors such as dry mouth and loss of water from tissues. By the end of the 19th century, physiologists proposed a thirst center in the brain that was verified in animals 60 years later. During the early- and mid-1900s, the influences of gastric distention, neuroendocrine responses, circulatory properties (i.e., blood pressure, volume, concentration), and the distinct effects of intracellular dehydration and extracellular hypovolemia were recognized. The majority of these studies relied on animal models and laboratory methods such as microinjection or lesioning/oblation of specific brain loci. Following a quarter century (1994–2019) of human brain imaging, current research focuses on networks of networks, with thirst and satiety conceived as hemispheric waves of neuronal activations that traverse the brain in milliseconds. Novel technologies such as chemogenetics, optogenetics, and neuropixel microelectrode arrays reveal the dynamic complexity of human thirst, as well as the roles of motivation and learning in drinking behavior.

Inputs to Thirst and Drinking during Water Restriction and Rehydration

“…Measurements assessed body fluid volume/concentration, dietary intake, renal responses, drinking behavior, and ratings of subjective perceptions. In this way, the present investigation provides important context regarding the central integration of information, as identified in animal models and previously published human brain imaging studies [12].…”

“…If this threshold did not exist, cognitive attention would be aroused by minor deviations from baseline, and other physiologically important behaviors would be minimized by a constant preoccupation with thirst [21]. In fact, multiple controlled laboratory studies have determined the plasma osmolality at which human thirst is perceived [22,23], but a precise universal threshold cannot be generalized to all individuals because it varies by sex (men, women), menstrual cycle phases (follicular, luteal), and twin types (monozygotic, dizygotic [12]). Indeed, when test subjects left their daily activities on Day 1 and returned to the HPL because they had become aware of thirst (Table 3), mean plasma osmolality had risen from the baseline value of 296 ± 4 to 298 ± 4 mOsm/kg, indicating that the plasma osmolality threshold for the onset of thirst had been reached.…”

“…Although our current understanding of the brain's conversion of subconscious homeostatic signals and conscious subjective perceptions into motivation and drinking behavior is inadequate (Figure 4), we propose three possible explanations as to why the volume of water consumed in a hypohydrated, relatively thirsty state was not correlated with thirst, other VAS ratings, or homeostatic variables (i.e., plasma osmolality, body mass change). (1) Drinking behavior is the result of a diverse neural network that is not identical to the one that potentiates and extinguishes thirst [3,12,27]. Indeed, indescribable complexity was the exact conclusion drawn from an assessment of primate water intake that was electrically stimulated at 5885 forebrain loci.…”

“…Thus, perceived thirst is centrally integrated with subconscious autonomic neuroendocrine responses [6][7][8] to maintain a narrow physiological range of body fluid osmolality, volume, and blood pressure [9]. In addition to thirst, other conscious perceptions influence drinking behavior and the control of vasopressin; originating as neural signals from the oropharyngeal region and gut [10,11], they are perceived as mouth dryness or wetness and stomach emptiness or distention [12,13].…”

Thirst as an ingestive behavior: A brief review on physiology and assessment

“…Experiments have spanned from intravenous infusion of water to alleviate the thirst of dogs, to isotonic fluid in which to assuage the intense thirst of cholera, to a man who was kicked in the head by a horse and consumed 3 L of beer and water in three hours (Blass, 1975). From these unique experiments and cases, the field of ingestive behavior has made tremendous strides to now be able to locate the central and peripheral receptors that satiate thirst (Armstrong and Kavouras, 2019; Augustine et al, 2019; Zimmerman et al, 2019).…”